Genomes and Genes
mitogen activated protein kinase kinases
Summary: A serine-threonine protein kinase family whose members are components in protein kinase cascades activated by diverse stimuli. These MAPK kinases phosphorylate MITOGEN-ACTIVATED PROTEIN KINASES and are themselves phosphorylated by MAP KINASE KINASE KINASES. JNK kinases (also known as SAPK kinases) are a subfamily.
- Chotiner J, Nielson J, Farris S, Lewandowski G, Huang F, Banos K, et al. Assessment of the role of MAP kinase in mediating activity-dependent transcriptional activation of the immediate early gene Arc/Arg3.1 in the dentate gyrus in vivo. Learn Mem. 2010;17:117-29 pubmed publisher..1 transcription in dentate granule cells in vivo is mediated in part by MAP kinase activation, but other signaling pathways also contribute, especially in the case of Arc/Arg3.1 induction in response to experience. ..
- Thivierge M, Stankova J, Rola Pleszczynski M. Cysteinyl-leukotriene receptor type 1 expression and function is down-regulated during monocyte-derived dendritic cell maturation with zymosan: involvement of IL-10 and prostaglandins. J Immunol. 2009;183:6778-87 pubmed publisher..This effect is partially dependent on an endogenous production of PGs and IL-10 by DCs. ..
- Gobbi G, Ricci F, Malinverno C, Carubbi C, Pambianco M, Panfilis G, et al. Hydrogen sulfide impairs keratinocyte cell growth and adhesion inhibiting mitogen-activated protein kinase signaling. Lab Invest. 2009;89:994-1006 pubmed publisher..In agreement with the in vitro observations, the immunohistochemical analysis of patient biopsies showed a specific downregulation of ERK activation levels, the key molecular event in the sulfur-induced effects on keratinocytes. ..
- Phoenix T, Temple S. Spred1, a negative regulator of Ras-MAPK-ERK, is enriched in CNS germinal zones, dampens NSC proliferation, and maintains ventricular zone structure. Genes Dev. 2010;24:45-56 pubmed publisher..Thus, Spred1 is critical for normal cortical development, as it modulates progenitor self-renewal/proliferation and helps maintain the integrity and organization of germinal zones. ..
- Mansell J, Farrar D, Jones S, Nowghani M. Cytoskeletal reorganisation, 1alpha,25-dihydroxy vitamin D3 and human MG63 osteoblast maturation. Mol Cell Endocrinol. 2009;305:38-46 pubmed publisher..Herein we describe how the signalling elicited via microtubule disruption cooperates with D3 in the development of mature osteoblasts. ..
- Kim S, Kim J, Choi I, Kim D, Kim M, An H, et al. Anti-inflammatory activity of Schizonepeta tenuifolia through the inhibition of MAPK phosphorylation in mouse peritoneal macrophages. Am J Chin Med. 2008;36:1145-58 pubmed..Taken together, the results of this study suggest an important molecular mechanism by which ST reduces inflammation, which may explain its beneficial effect in the regulation of inflammatory reactions. ..
- Jang B, Park J, Song D, Baek W, Yoo S, Jung K, et al. Sanguinarine induces apoptosis in A549 human lung cancer cells primarily via cellular glutathione depletion. Toxicol In Vitro. 2009;23:281-7 pubmed publisher..These results collectively suggest that sanguinarine induces apoptosis in A549 cells through cellular glutathione depletion and the subsequent caspase activation. ..
- Du F, Xu J, Zhang J, Gao S, Carter M, He C, et al. Beneficial effect of young oocytes for rabbit somatic cell nuclear transfer. Cloning Stem Cells. 2009;11:131-40 pubmed publisher..7 % (n = 117) (Experiment 4). These results demonstrated that NT utilizing relatively young rabbit oocytes, harvested at 10-12 h after hCG injection, was beneficial for the development of NT embryos. ..
- Pellegrini M, Filipponi D, Gori M, Barrios F, Lolicato F, Grimaldi P, et al. ATRA and KL promote differentiation toward the meiotic program of male germ cells. Cell Cycle. 2008;7:3878-88 pubmed..These data suggest that RA may control the timing of meiosis by influencing both the somatic and the germ cell compartment of the postnatal testis through the activation of the KL/Kit system. ..
- Gupta G, Bhattacharjee S, Bhattacharyya S, Bhattacharya P, Adhikari A, Mukherjee A, et al. CXC chemokine-mediated protection against visceral leishmaniasis: involvement of the proinflammatory response. J Infect Dis. 2009;200:1300-10 pubmed publisher..Thus, this study strongly demonstrates that IP-10, like CC chemokines, is involved in rendering a protective response in visceral leishmaniasis via up-regulation of proinflammatory mediators...
- Yamnik R, Holz M. mTOR/S6K1 and MAPK/RSK signaling pathways coordinately regulate estrogen receptor alpha serine 167 phosphorylation. FEBS Lett. 2010;584:124-8 pubmed publisher..We report that the mTOR/S6K1 and MAPK/RSK contribute non-overlapping inputs into ERalpha activation via Ser167 phosphorylation. This cooperation may be targeted in breast cancer treatment by a combination of mTOR and MAPK inhibitors. ..
- Zhang Y, Yu G, Xiang Y, Wu J, Jiang P, Lee W, et al. Bm-TFF2, a toad trefoil factor, promotes cell migration, survival and wound healing. Biochem Biophys Res Commun. 2010;398:559-64 pubmed publisher..The potent biological activity of Bm-TFF2 makes it a useful molecular tool for further studies of structure-function relationship of the related human TFFs. ..
- Basu A, Hoerning A, Datta D, Edelbauer M, Stack M, Calzadilla K, et al. Cutting edge: Vascular endothelial growth factor-mediated signaling in human CD45RO+ CD4+ T cells promotes Akt and ERK activation and costimulates IFN-gamma production. J Immunol. 2010;184:545-9 pubmed publisher..Collectively, our results for the first time define a novel function for VEGF and KDR in CD45RO+ memory T cell responses that are likely of great pathophysiological importance in immunity. ..
- Jin Y, Cui X, Han Y, Kim N. Leptin accelerates pronuclear formation following intracytoplasmic sperm injection of porcine oocytes: Possible role for MAP kinase inactivation. Anim Reprod Sci. 2009;115:137-48 pubmed publisher..These results suggested that exogeneous leptin enhanced spindle assembly and accelerated pronuclear formation following fertilization, possibly via the MAPK pathway. ..
- Sathishkumar K, Yallampalli U, Elkins R, Yallampalli C. Raf-1 kinase regulates smooth muscle contraction in the rat mesenteric arteries. J Vasc Res. 2010;47:384-98 pubmed publisher..The results indicate that Raf-1 kinase plays an important role in the regulation of vascular contractility through regulation of calcium sensitization. ..
- Mitchell C, Joyce A, Piper J, McKallip R, Fariss M. Role of oxidative stress and MAPK signaling in reference moist smokeless tobacco-induced HOK-16B cell death. Toxicol Lett. 2010;195:23-30 pubmed publisher..Thus, acute exposure to STE leads to HOK-16B cell death in part through oxidative stress via activation of ASK1 and the JNK1/2 and p38 MAPK pathways. ..
- Abrams S, Steelman L, Shelton J, Wong E, Chappell W, Basecke J, et al. The Raf/MEK/ERK pathway can govern drug resistance, apoptosis and sensitivity to targeted therapy. Cell Cycle. 2010;9:1781-91 pubmed..These results indicate that targeting the Raf/MEK/ERK and PI3K/Akt/mTOR pathways may be an effective approach for therapeutic intervention in drug resistant cancers that have mutations activating these cascades. ..
- Hamdi M, Mutungi G. Dihydrotestosterone activates the MAPK pathway and modulates maximum isometric force through the EGF receptor in isolated intact mouse skeletal muscle fibres. J Physiol. 2010;588:511-25 pubmed publisher..These are mediated through the EGF receptor and one of their main physiological functions is the enhancement of force production in fast twitch skeletal muscle fibres...
- Ji C, Yang Y, Yang B, Xia J, Sun W, Su Z, et al. Trans-Zeatin attenuates ultraviolet induced down-regulation of aquaporin-3 in cultured human skin keratinocytes. Int J Mol Med. 2010;26:257-63 pubmed..MEK/ERK activation is involved in this process. tZ treatment attenuates UV-induced AQP3 loss, in vitro wound healing delay and water permeability decrease. This work provides a new explanation for the anti-photoaging potential of tZ. ..
- Elzinga B, Twomey C, Powell J, Harte F, McCarthy J. Interleukin-1 receptor type 1 is a substrate for gamma-secretase-dependent regulated intramembrane proteolysis. J Biol Chem. 2009;284:1394-409 pubmed publisher..These findings also suggest that regulated intramembrane proteolysis may be a control mechanism for IL-1R1-mediated signaling. ..
- Cuesta Mateos C, López Giral S, Alfonso Pérez M, de Soria V, Loscertales J, Guasch Vidal S, et al. Analysis of migratory and prosurvival pathways induced by the homeostatic chemokines CCL19 and CCL21 in B-cell chronic lymphocytic leukemia. Exp Hematol. 2010;38:756-64, 764.e1-4 pubmed publisher..The role of PI3K, Rho guanosine triphosphatases, and MAPKs in CCR7-mediated CLL cells migration and survival suggests that these signal transduction pathways could represent promising targets for CLL therapy. ..
- Smirnova I, Chang S, Forsthuber T. Prosurvival and proapoptotic functions of ERK1/2 activation in murine thymocytes in vitro. Cell Immunol. 2010;261:29-36 pubmed publisher..Thus, ERK1/2 has a dual role in promoting cell survival and cell death in thymocytes in the context of different stimuli. ..
- Dilly M, Hambruch N, Haeger J, Pfarrer C. Epidermal growth factor (EGF) induces motility and upregulates MMP-9 and TIMP-1 in bovine trophoblast cells. Mol Reprod Dev. 2010;77:622-9 pubmed publisher..In conclusion, EGF-mediated effects stimulate migration and proliferation of bovine trophoblast cells and may be involved in bovine placental tissue remodeling and postpartum release of fetal membranes. ..
- Ocio E, Mateos M, Maiso P, Pandiella A, San Miguel J. New drugs in multiple myeloma: mechanisms of action and phase I/II clinical findings. Lancet Oncol. 2008;9:1157-65 pubmed publisher..Unfortunately, the single-agent clinical activity of most of these new drugs has been limited; nevertheless, their effectiveness might be enhanced by their rational combination with each other or with conventional agents. ..
- Kao E, Hsu J, Wang C, Yang S, Cheng S, Lee H. Polyphenols extracted from Hibiscus sabdariffa L. inhibited lipopolysaccharide-induced inflammation by improving antioxidative conditions and regulating cyclooxygenase-2 expression. Biosci Biotechnol Biochem. 2009;73:385-90 pubmed..The study also revealed that down-regulation of cyclooxygenase-2 (COX-2), p-c-Jun N-terminal kinase (p-JNK) and p-P38 might have been involved. In sum, this study found an anti-inflammatory potency of HPE both in vitro and in vivo...
- Piltonen M, Bespalov M, Ervasti D, Matilainen T, Sidorova Y, Rauvala H, et al. Heparin-binding determinants of GDNF reduce its tissue distribution but are beneficial for the protection of nigral dopaminergic neurons. Exp Neurol. 2009;219:499-506 pubmed publisher..The results imply that GDNF binding to HSs is needed for the optimum neuroprotective effect. ..
- Kuang E, Wu F, ZHU F. Mechanism of sustained activation of ribosomal S6 kinase (RSK) and ERK by kaposi sarcoma-associated herpesvirus ORF45: multiprotein complexes retain active phosphorylated ERK AND RSK and protect them from dephosphorylation. J Biol Chem. 2009;284:13958-68 pubmed publisher..Finally, we provide evidence that this mechanism contributes to the sustained activation of ERK and RSK in Kaposi sarcoma-associated herpesvirus lytic replication. ..
- Zeng S, Dun H, Ippagunta N, Rosario R, Zhang Q, Lefkowitch J, et al. Receptor for advanced glycation end product (RAGE)-dependent modulation of early growth response-1 in hepatic ischemia/reperfusion injury. J Hepatol. 2009;50:929-36 pubmed publisher..Suppression of Egr-1 may contribute to the protective mechanisms underlying the beneficial impact of RAGE blockade or deletion. ..
- Xu Y, Bismar T, Su J, Xu B, Kristiansen G, Varga Z, et al. Filamin A regulates focal adhesion disassembly and suppresses breast cancer cell migration and invasion. J Exp Med. 2010;207:2421-37 pubmed publisher..These results document a regulation of FA dynamics by FLNa in breast cancer cells. ..
- Cai S, Batra S, Shen L, Wakamatsu N, Jeyaseelan S. Both TRIF- and MyD88-dependent signaling contribute to host defense against pulmonary Klebsiella infection. J Immunol. 2009;183:6629-38 pubmed publisher..pneumoniae infection in the lungs and demonstrate the therapeutic potential of MyD88 in reducing excessive neutrophil influx in human disease during Gram-negative bacterial pneumonia. ..
- Tencheva T, Panov I. Intracerebral development of transplanted glioblastoma C6 cells in rats after preliminary exposure to neuropeptides and an MAPK inhibitor. Neurosci Behav Physiol. 2008;38:913-6 pubmed publisher..Endothelin-1 significantly increased the proliferation of glioma C6 cells. The model used in this study was experimental and may allow the specific features of the in vitro behavior of cultured invasive cells to be identified. ..
- Niwa M, Nitta A, Cen X, Kitaichi K, Ozaki N, Yamada K, et al. A novel molecule 'shati' increases dopamine uptake via the induction of tumor necrosis factor-alpha in pheochromocytoma-12 cells. J Neurochem. 2008;107:1697-708 pubmed publisher..These results suggest that the functional roles of shati in METH-regulated behavioral changes are mediated through inhibition of the METH-induced decrease in DA uptake via TNF-alpha. ..
- Cho K, Agrawal G, Jwa N, Kubo A, Rakwal R. Rice OsSIPK and its orthologs: a "central master switch" for stress responses. Biochem Biophys Res Commun. 2009;379:649-53 pubmed publisher..In this minireview, we discuss the recent progress on rice OsSIPK and its orthologs as a "central master switch" for mediating plant responses against ozone, wounding, and JA as examples. ..
- Yip Schneider M, Klein P, Wentz S, Zeni A, Menze A, Schmidt C. Resistance to mitogen-activated protein kinase kinase (MEK) inhibitors correlates with up-regulation of the MEK/extracellular signal-regulated kinase pathway in hepatocellular carcinoma cells. J Pharmacol Exp Ther. 2009;329:1063-70 pubmed publisher..Our findings also provide preclinical evidence suggesting that the status of the MEK/ERK pathway in patients may predict response to MEK/ERK-targeted therapeutics. ..
- Bajwa A, Jo S, Ye H, Huang L, Dondeti K, Rosin D, et al. Activation of sphingosine-1-phosphate 1 receptor in the proximal tubule protects against ischemia-reperfusion injury. J Am Soc Nephrol. 2010;21:955-65 pubmed publisher..Selective agonists of S1P1Rs may hold therapeutic potential for the prevention and treatment of acute kidney injury. ..
- Peng J, Yuan Q, Lin B, Panneerselvam P, Wang X, Luan X, et al. SARM inhibits both TRIF- and MyD88-mediated AP-1 activation. Eur J Immunol. 2010;40:1738-47 pubmed publisher..Finally, we provide evidence to show that truncated SARM changes its subcellular localization, suggesting the importance of the N-terminal and sterile alpha motif domains in the autoregulation of SARM activity. ..
- Karagounis L, Yaspelkis B, Reeder D, Lancaster G, Hawley J, Coffey V. Contraction-induced changes in TNFalpha and Akt-mediated signalling are associated with increased myofibrillar protein in rat skeletal muscle. Eur J Appl Physiol. 2010;109:839-48 pubmed publisher..Indeed, the cumulative effect of these signalling events was associated with myofibrillar protein accretion, which likely contributes to the early adaptations in response to resistance training overload in the skeletal muscle. ..
- Jiang Q, Cao C, Lu S, Kivlin R, Wallin B, Chu W, et al. MEK/ERK pathway mediates UVB-induced AQP1 downregulation and water permeability impairment in human retinal pigment epithelial cells. Int J Mol Med. 2009;23:771-7 pubmed..Our results further support the notion that all-trans retinoic acid might be useful for protection against UV or oxidative stress-induced eye cell damage...
- Bartels S, Anderson J, González Besteiro M, Carreri A, Hirt H, Buchala A, et al. MAP kinase phosphatase1 and protein tyrosine phosphatase1 are repressors of salicylic acid synthesis and SNC1-mediated responses in Arabidopsis. Plant Cell. 2009;21:2884-97 pubmed publisher..Our data thus indicate a major role of MKP1 and PTP1 in repressing salicylic acid biosynthesis in the autoimmune-like response caused by SNC1. ..
- Quan H, Liu H, Li C, Lou L. 1,4-Diamino-2,3-dicyano-1,4-bis(methylthio)butadiene (U0126) enhances the cytotoxicity of combretastatin A4 independently of mitogen-activated protein kinase kinase. J Pharmacol Exp Ther. 2009;330:326-33 pubmed publisher..It is most important to note that these findings indicate that the combination of CA4 with inhibitors of glucuronidation may be a novel and rational strategy for cancer therapy. ..
- Liu L, Chen B, Qin S, Li S, He X, Qiu S, et al. A novel histone deacetylase inhibitor Chidamide induces apoptosis of human colon cancer cells. Biochem Biophys Res Commun. 2010;392:190-5 pubmed publisher..Our data support the potential application of Chidamide as an anticancer agent in treating colon cancer. Future studies are needed to demonstrate its in vivo efficacy. ..
- Kaisman Elbaz T, Sekler I, Fishman D, Karol N, Forberg M, Kahn N, et al. Cell death induced by zinc and cadmium is mediated by clusterin in cultured mouse seminiferous tubules. J Cell Physiol. 2009;220:222-9 pubmed publisher..Taken together, our results indicate that Zn(2+) and Cd(2+) influx induce expression and secretion of clusterin, thereby linking metal homeostasis and germ cell fate...
- Kim S, Cho S, Kim K, Shin K, Kim H, Park C, et al. Alpha-synuclein induces migration of BV-2 microglial cells by up-regulation of CD44 and MT1-MMP. J Neurochem. 2009;109:1483-96 pubmed publisher..With the recruitment of the microglial population into the SNpc during dopaminergic neurodegeneration, alpha-synuclein may play a role in accelerating the pathogenesis of PD. ..
- Pan C, Olsen J, Daub H, Mann M. Global effects of kinase inhibitors on signaling networks revealed by quantitative phosphoproteomics. Mol Cell Proteomics. 2009;8:2796-808 pubmed publisher..Our assay is streamlined and generic and could become a useful tool in kinase drug development. ..
- Theoleyre S, Mottier S, Masson D, Denis M. HtrA3 is regulated by 15-deoxy-Delta12,14-prostaglandin J2 independently of PPARgamma in clear cell renal cell carcinomas. Biochem Biophys Res Commun. 2010;394:453-8 pubmed publisher..Our results provide a better understanding of the mechanisms involved in the regulation of HtrA3, a potential tumor suppressor gene. ..
- Younes Rapozo V, Felgueiras L, Viana N, Fierro I, Barja Fidalgo C, Manhães A, et al. A role for the MAPK/ERK pathway in oligodendroglial differentiation in vitro: stage specific effects on cell branching. Int J Dev Neurosci. 2009;27:757-68 pubmed publisher..These data showed an effect of the MAPK/ERK pathway on oligodendroglial branching, with possible consequences for the formation of the myelin sheath. ..
- Gao Z, Ding Y, Jacobson K. UDP-glucose acting at P2Y14 receptors is a mediator of mast cell degranulation. Biochem Pharmacol. 2010;79:873-9 pubmed publisher..Thus, mast cells express an endogenous P2Y(14) receptor, which mediates G(i)-dependent degranulation and is therefore a potential novel therapeutic target for allergic conditions. ..
- Pham H, Chen M, Li A, King J, Angst E, Dawson D, et al. Loss of 15-hydroxyprostaglandin dehydrogenase increases prostaglandin E2 in pancreatic tumors. Pancreas. 2010;39:332-9 pubmed publisher..These results suggest that enhanced PGE2 production proceeds through the expressions of COX-2 and microsomal PGES-1 and down-regulation of PGDH by SNAI2 in pancreatic tumors. ..